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Mechanism of senescence in human cells - multistep alterations in genes involved in senescence

Research Project

Project/Area Number 09470406
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionThe Nippon Dental University

Principal Investigator

TSUTSUI Takeki  The Nippon Dental University, School of Dentistry at Tokyo, Professor, 歯学部, 教授 (00097065)

Co-Investigator(Kenkyū-buntansha) TAMURA Yukiko  The Nippon Dental University, School of Dentistry at Tokyo, Instructor, 歯学部, 助手 (20281438)
HASEGAWA Koko  The Nippon Dental University, School of Dentistry at Tokyo, Assistant Professor, 歯学部, 講師 (70053014)
関口 みずき  日本歯科大学, 歯学部, 助手 (10281437)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥11,900,000 (Direct Cost: ¥11,900,000)
KeywordsSenescence / Immortalization / Senescence gene / Human cells
Research Abstract

Five immortal cell lines derived from a Li-Fraumeni syndrome patient (MDAH 087) with a germline mutant p53 allele were characterized with respect to telomere length and genomic instability. The remaining wild type p53 allele is lost in the cell lines. Telomerase activity was undetectable in all immortal cell lines. Five subclones of each cell line and five re-subclones of each of the subclones also showed undetectable telomerase activity. The genes encoding the protein component (hTEP1) and the RNA component (hTERC) of telomerase were expressed in all the immortal cell lines, but the gene for telomerase reverse transcriptase (hTERT) was not. All five immortal cell lines exhibited variability in the mean length of terminal restriction fragments (TRFs). Five subclones of each cell line, and re-subclones of the subclones also showed TRF variability. Chromosome aberrations were observed at high frequencies in these cell lines including the subclones and re-subclones, and the principal type … More s of aberrations were breaks, double minute chromosomes and dicentric chromosomes. Estimated population doublings of the subclones or re-subclones after subcloning or re-subcloning were 22 to 24 population doublings when they were analyzed for TRF length and chromosome aberrations. The results indicate that TRF length variability and chromosome instability are intrinsic characteristics of the telomerasenegative immortal cell lines and occur in a short period. In addition, minisatellite alterations detected by DNA fingerprints were observed in all the immortal cell lines. However, all of the cell lines were negative for microsatellite instability. Tumor-derived human cell lines, HT1080 cells and Hela cells lacking p53 function, exhibited little genomic instability involving chromosomal and minisatellite instabilities. This indicates that the intrinsic features observed in the immortal cell lines lacking telomerase activity could not refult from loss of p53 function. The immortal cell lines may be useful for studying the mechanism associated between telomere maintenance in telomerase-negative cells and genomic instability, particularly involvinge gene amplification and/or recombination. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Tsutsui, T.: "17 β-estradiol, diethylstilbestrol, tamoxifen, toremifene and ICI 164, 384 induce morphological transformation and aneuploidy in cultured Syrian hamster embryo cells"Int.J.Cancer. 70. 188-193 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Extended life span and immortalization of human fibroblasts induced by X-ray irradiation"Mol. Carcinogenesis. 18. 7-18 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Benzene-, catechol-, hydroquinone- and phenol-induced cell transformation, gene mutations, chromosome aberrations, a neuploidy, sister chromatid exchanges and unscheduled DNA synthesis in Syrian hamster embryo cells"Mutat. Res.. 373. 113-123 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals"Environ. Health. Perspect.. 105. 619-624 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 井川淳一: "ヒト歯肉上皮およびヒト歯肉由来培養ケラチノサイトの細胞死における核の形態学変化"日口外誌. 43. 383-393 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "培養哺乳類細胞によるエストロゲンのがん化機構の研究-^<32>P-ポストラベリング法によるDNA付加体の検出-"日薬理誌. 110. 1-9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "In vitro cytotoxicity of diverse preparations used in dental practice to human gingival keratinocytes"Toxic. In Vitro. 11. 393-398 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Cell-transformation activity and genotoxicity of phenolphthalein in cultured Syrian hamster embryo cells"Int. J. Cancer. 73. 697-701 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "わかりやすい"癌細胞"への道のり"日歯医師会誌. 50. 963-970 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Bisphenol-A induces cellular transfomation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells"Int. J. Cancer. 75. 290-294 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kumakura, S.: "Loss of heterozygosity on chromosome 6 in immortal human fibroblasts"J. Nippon Dent. Univ.. 1. 16-19 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kawakami, T.: "Inhibition by 17 β-estradiol of interleukin-1 α production of cultured human diploid fibroblasts"J.Nippon Dent.Univ.. 1. 33-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 五十嵐史征: "Origin(-)SV40遺伝子とc-fos遺伝子の移入によるヒト歯肉由来培養ケラチノサイトの不死化とその性状"歯学. 86. 37-47 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuchiya, T.: "An interlaboratory validation study of the improve transformation assay employing Balb/c 3T3 cells : Results of a collaborative study on the two-stage cell transformation assay by the non-genotoxic carcinogen study group"ATLA. 27. 685-702 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Omori, N.: "Quantitative comparison of cytocidal effects of tetracyclines and fluoroquinolones on human periodontal ligament fibroblasts"J.Periodont. Res. 34. 290-295 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Involvement of genotoxic effects in the initiation of estrogen-induced cellular transformation : studies using Syrian hamster embryo cells treated with 17β-estradiol and eight of its metabolites"Int. J. Cancer. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Mammalian cell transformation and aneuploidy induced by five bisphenols"Int. J. Cancer. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T.: "Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen"Carcinogenesis. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "歯科薬理学(第4版)"医師薬出版. 7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "歯科医学・歯科保健医療各論 下巻"日本歯科大学「歯科医学・歯科保健医療各論」検討委員会. 15 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "歯科薬物療法総論"一世出版. 106 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "新常用歯科辞典(第3版)"医師薬物版. 1440 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井健機: "新歯科薬理学入門"一世出版. 185 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsuchiya, T. et al.: "An intelaboratory validation study of the improve transformation assay employing Balb/c 3T3 cells : Results of a collaborative study on the two-stage cell transformation assay by the non-genotoxic carcinogen study group."ATLA. 27. 685-702 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Omori, N. et al.: "Quantitative comparison of cytocidal effects of tetracyclines and fluoroquinolones on human periodontal ligament fibroblasts."J. Periodont. Re.. 34. 290-295 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T. et al.: "Involvement of genotoxic effects in the initiation of estrogen-induced cellular transformation : studies using Syrian hamster embryo cells treated with 17β-estradiol and eight of its metabolites."Int. J. Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T. et al.: "Mammalian cell transformation and aneuploidy induced by five bisphenols."Int. J. Cancer. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsutsui, T. et al.: "Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen."Carcinogenesis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 筒井 健機: "今、遺伝子はここまでわかってきた-予知遺伝子検査による病気の予測"日歯医師会誌. 51・10. 1007-1014 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsuchiya, T.: "An interlaboratory validation study of the improve transformation assay employing Balb/c 3T3 cells: Results of a collaborative study on the two-stage cell transformation assay by the non-genotoxic carcinogen study group."ATLA. 27. 685-702 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Omori, N.: "Quantitative comparison cytocidal effects of tetracyclines and fluoroquinolones on human periodontal ligament fibroblasts."J. Periodont. Res.. 34. 290-295 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsutsui, T.: "Involvement of genotoxic effects in the initiation of estrogen-induced cellular transformation: studies using Syrian hamster embryo cells treated with 17 β-estradiol and eight of its metabolites."Int. J. Cancer. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsutsui, T.: "Mammalian cell transformation and aneuploidy induced by five bisphenols."Int. J. Cancer. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsutsui, T.: "Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen."Caricinogenesis. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 中原 泉: "新常用歯科辞典"医歯薬出版. 1410 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筒井 健機: "新歯科薬理学入門"一世出版. 185 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 筒井健機: "わかりやすい“がん細胞"への道のり" 日歯医師会誌. 50(10). 963-970 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsutsui,T.: "Bisphenol-A induces cellular transformation,aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells." Int.J.Cancer. 75(2). 290-294 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 佐藤英継: "ヒト歯肉由来培養ケラチノサイトにおけるテトラサイクリン系抗生物質の細胞生存率と細胞内濃度に及ぼす効果" 日歯周誌. 40(1). 1-8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kumakura,S.: "Loss of heterozygosity on chromosome 6 in immortal human fibroblasts." J.Nippon Dent.Univ.1. 16-19 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kawakami,T.: "Inhibition by 17 β-estradiol of interleukin-1α production of cultured human diploid fibroblasts." J.Nippon Dent.Univ.1. 33-39 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 五十嵐史征: "Origin(-)SV40遺伝子とc-fos遺伝子の移入によるヒト歯肉由来培養ケラチノサイトの不死化とその性状" 歯学. 86(1). 37-47 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 筒井健機: "シリアン・ハムスター胎仔(SHE)細胞による非変異原性がん原物質のがん化機構の解析" 環境変異原研究. 20(2). 137-148 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 上濱 正: "塩酸ミノサイクリンのヒト歯根膜由来培養線維芽細胞に対する作用について" 歯学. 86(2). 320-328 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 筒井健機: "今,遺伝子はここまでわかってきた-予知遺伝子検査による病気の予測-" 日歯医師会誌. 51(10). 1007-1014 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 筒井健機: "(株)一世出版" 歯科薬物療法総論, 76 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tsutsui,T.: "17 β -Estradiol,diethylstilbestrol,tamoxifen,toremifene and ICI 164,384 induce morphological transformation and aneuploidy in cultured Syrian hamster・ ・ ・" Int.J.Cancer. 70. 193 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutsui,T.: "Extended lifespan and immortalization of human fibroblasts induced by X-ray irradiation" Mol.Carcinogenesis. 18(1). 7-18 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutsui,T.: "Benzene-,catechol-,hydroquinone- and phenol-induced cell transformation,gene mutations,chromosome aberrations,aneuploidy,・ ・ ・ ・" Mutation Res.373(1). 113-123 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 筒井健機: "生体の防御機構の多様性" 歯界展望. 89(4). 878-888 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tsutsui,T.: "Neoplastic transformation of cultured mammalian cells by estrogens and estrogenlike chemicals" Envion.Health Perspect.105. 619-624 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 井川淳一: "ヒト歯肉上皮およびヒト歯肉由来培養ケラチノサイトの細胞死における核の形態学的変化" 日口外誌. 43(5). 383-393 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 筒井健機: "歯科薬理学" 医歯薬出版, 541 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 筒井健機: "歯科医学・歯科保健医療各論" デンタルフォーラム, 773 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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